This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cell development in higher organisms is controlled in part by communication between the nucleus and the surrounding extracellular environment, and accumulating evidence shows that changes in the structure of a cell''''s genetic material are central to the regulation of this communication. The inability of the extracellular environment to communicate properly with the nucleus is one of the hallmarks of tumor development. We have developed a model system in which normal mammary epithelial cells respond to a physiologically relevant three-dimensional, laminin-rich basement membrane (IrBM) by undergoing a functional differentiation. This assay will be used to determine how the extracellular environment influences the structure and organization of a cell's genetic material in a manner that regulates the expression of specific genes. To identify these changes, we will employ a combination of biochemical and microscopy techniques. Characterizing the role of the extracellular environment on mammary cell development will contribute towards a better understanding of normal breast cell development and gene expression and may also have implications for breast tumorigenesis and disease intervention.